A major obstacle to the wide application of implantable glucose sensors is that the progressively lose function after a relatively short period of time in vivo. This is a result of tissue responses such as inflammation and fibrosis with resulting loss of vasculature as well as degradation of the sensor. Although our current Nafion-based glucose sensor displayed excellent stability in vitro, it rapidly calcified and degraded in vivo. The investigator hypothesizes that in vivo sensor performance can be enhanced by developing new membranes and by controlling the tissue interface by suppressing inflammation and fibrosis as well as increasing neovascularization. Aim 1 will develop new membranes to replace Nafion, and also to develop novel surface hydrogels with tissue response modifiers (TRM's) to control fibrosis, inflammation, and neovascularization. Aim 2 will develop biodegradable TRM delivery systems to control inflammation, fibrosis and neovascularization. Aim 3 will evaluate in vitro and in vivo (rats), the developed sensors and components to determine performance, including life span.